A PHASE I IB TRIAL OF MURINE MONOCLONAL ANTI-GD2 ANTIBODY 14.G2A PLUSINTERLEUKIN-2 IN CHILDREN WITH REFRACTORY NEUROBLASTOMA - A REPORT OFTHE CHILDRENS CANCER GROUP/

BACKGROUND. The murine monoclonal antibody (MoAb) 14.G2a recognizes GD 2, a disialoganglioside expressed in tumors of neuroectodermal origin, and facilitates antibody dependent cellular cytotoxicity (ADCC) in vi tro. When given in vivo, interleukin-2 (IL-2) can increase ADCC by enh ancing the activity and number of circulating lymphocytes. METHODS. Th irty-three pediatric patients with GD2 positive malignancies, ranging in age from 2 to 17 years (median, 9.9 years), received IL-2 and 14.G2 a in this Phase I/IB study of the Children's Cancer Group (CCG) and we re monitored for toxicities and response to therapy. Seven of these pa tients also received granulocyte-macrophage-colony stimulating factor. RESULTS. The maximum tolerated dose (MTD) of 14.G2a with IL-2 was 15 mg/m(2)/day. The most prevalent Grade 3-4 toxicities were generalized pain (n = 14 [42%]) and fever without documented infection (n = 17 [52 %]). IL-2 was thought to be the causative agent in most cases of fever . Toxicities attributed to 14.G2a included pain, allergic or anaphylac tic reactions, and rash. Human antimouse antibodies were demonstrated in 9 of 21 evaluated patients. One patient with neuroblastoma had a pa rtial response, and one patient with osteosarcoma had a complete respo nse. Immunocytology demonstrated that the number of neuroblastoma cell s in bone marrow decreased in three patients. CONCLUSIONS. The murine MoAb 14.G2a was well tolerated at the MTD and appeared to have some an titumor activity. Further development of this approach will involve ad ditional engineered forms of the antibody as well as testing in the ad juvant and minimal residual disease setting. (C) 1997 American Cancer Society.